Glucocorticoid hormones appear to regulate the posttranslational processing and compartmentalization of mouse mammary tumor virus (MTV) glycoproteins and phosphoproteins in infected cultured rat hepatoma (HTC) cells. The detection of this novel regulatory circuit implies that general physiological regulators, such as steroid hormones, can affect the expression of specific genes long after they have been transcribed. The following genetic and biochemical approaches will be employed to define and characterize at a molecular level the cellular pathways involved with regulated polypeptide maturation. (A) A broad range of mutant MTV-infected HTC cells with defects in hormone regulated MTV protein maturation will be selected by procedures such as complement mediated cytolysis and cell column chromatography; (B) Various phenotypic classes will be distinguished by examining the hormone induced expression of MTV RNA and protein products while somatic cell hybridizations between appropriate combinations of mutant and/or wild type cells employed to define the minimum number of functional cellular elements; (C) Detailed biochemical comparisons of MTV polypeptides produced in mutant and wild type cells will explore precursor-product relationships, cellular site of appearance, polypeptide modifications and cellular requirements of these processes; (D) Mutant cell lines defective at different stages of polypeptide maturation will be exploited in attempts to devise an in vitro MTV protein maturation assay so that specific hormone regulated components can be detected and eventually isolated; and (E) long term objectives will extend some of the above approaches to other MTV-infected cell types to test the significance and generality of regulated protein maturation.